Electrocatalytic activity of symmetric and asymmetric Co(II) and Mn(III) porphyrins in the presence of graphene quantum dots towards the oxidation of hydrazine
- Authors: Jokazi, Mbulelo
- Date: 2022-10-14
- Subjects: Electrocatalysis , Hydrazine , Quantum dots , Graphene , Porphyrins
- Language: English
- Type: Academic theses , Master's theses , text
- Identifier: http://hdl.handle.net/10962/362894 , vital:65372
- Description: The influence of metal porphyrins in electro-oxidation of hydrazine is explored. A series of symmetric and asymmetric porphyrins alone and in the presence of graphene quantum dots (GQDs) are employed in this work. Tetra 4-aminophenyl porphyrin, manganese tetra 4-aminophenyl porphyrin, manganese tetra 4-aminophenyl porphyrin--GQDs, and manganese tetra 4-aminophenyl porphyrin@GQDs are the symmetric porphyrins. The asymmetric porphyrin and composites are 5, 10, 15-tris(aminophenyl)-20-(4-carboxyphenyl) porphyrins, manganese 5, 10, 15-tris(aminophenyl)-20-(4-carboxyphenyl) porphyrins, cobalt 5, 10, 15-tris(aminophenyl)-20-(4-carboxyphenyl) porphyrins, manganese 5, 10, 15-tris(aminophenyl)-20-(4-carboxyphenyl) porphyrins--GQDs, and cobalt 5, 10, 15-tris(aminophenyl)-20-(4-carboxyphenyl) porphyrins--GQDs. These complexes were synthesized and characterized accordingly and applied for electrocatalysis. The electrocatalytic experiments were carried out using glassy carbon electrode and the modification was through drop-dry method. The porphyrin and GQDs synthesized were characterized using UV-Vis spectroscopy, Mass spectrometry, X-ray diffraction, transmission electron microscopy, X-ray photoelectron spectroscopy and energy dispersive x-ray spectroscopy. The modified electrodes were characterized using cyclic voltammetry and electrochemical Impedance spectroscopy. The introduction of metal ion in the center of the porphyrin improved electrocatalysis. The presence of push-pull substituents in the porphyrin lowered the oxidation potential and improved the catalysis. The presence of GQDs improved catalysis in both symmetric and asymmetric porphyrin compared to individual components. Cobalt porphyrins showed better activity than manganese porphyrin. , Thesis (MSc) -- Faculty of Science, Chemistry, 2022
- Full Text:
- Date Issued: 2022-10-14
- Authors: Jokazi, Mbulelo
- Date: 2022-10-14
- Subjects: Electrocatalysis , Hydrazine , Quantum dots , Graphene , Porphyrins
- Language: English
- Type: Academic theses , Master's theses , text
- Identifier: http://hdl.handle.net/10962/362894 , vital:65372
- Description: The influence of metal porphyrins in electro-oxidation of hydrazine is explored. A series of symmetric and asymmetric porphyrins alone and in the presence of graphene quantum dots (GQDs) are employed in this work. Tetra 4-aminophenyl porphyrin, manganese tetra 4-aminophenyl porphyrin, manganese tetra 4-aminophenyl porphyrin--GQDs, and manganese tetra 4-aminophenyl porphyrin@GQDs are the symmetric porphyrins. The asymmetric porphyrin and composites are 5, 10, 15-tris(aminophenyl)-20-(4-carboxyphenyl) porphyrins, manganese 5, 10, 15-tris(aminophenyl)-20-(4-carboxyphenyl) porphyrins, cobalt 5, 10, 15-tris(aminophenyl)-20-(4-carboxyphenyl) porphyrins, manganese 5, 10, 15-tris(aminophenyl)-20-(4-carboxyphenyl) porphyrins--GQDs, and cobalt 5, 10, 15-tris(aminophenyl)-20-(4-carboxyphenyl) porphyrins--GQDs. These complexes were synthesized and characterized accordingly and applied for electrocatalysis. The electrocatalytic experiments were carried out using glassy carbon electrode and the modification was through drop-dry method. The porphyrin and GQDs synthesized were characterized using UV-Vis spectroscopy, Mass spectrometry, X-ray diffraction, transmission electron microscopy, X-ray photoelectron spectroscopy and energy dispersive x-ray spectroscopy. The modified electrodes were characterized using cyclic voltammetry and electrochemical Impedance spectroscopy. The introduction of metal ion in the center of the porphyrin improved electrocatalysis. The presence of push-pull substituents in the porphyrin lowered the oxidation potential and improved the catalysis. The presence of GQDs improved catalysis in both symmetric and asymmetric porphyrin compared to individual components. Cobalt porphyrins showed better activity than manganese porphyrin. , Thesis (MSc) -- Faculty of Science, Chemistry, 2022
- Full Text:
- Date Issued: 2022-10-14
Photodynamic antimicrobial chemotherapy against Staphylococcus aureus and Escherichia coli sensitized using indium (III) cationic porphyrins linked to core-shell magnetic nanoparticles
- Authors: Makola, Lekgowa Collen
- Date: 2021-04
- Subjects: Photochemotherapy , Photosensitizing compounds , Staphylococcus aureus , Escherichia coli , Indium , Porphyrins , Magnetic nanoparticles , Quaternize
- Language: English
- Type: thesis , text , Masters , MSc
- Identifier: http://hdl.handle.net/10962/177225 , vital:42801
- Description: Photodynamic antimicrobial chemotherapy (PACT) is a well-known antimicrobial therapy technique used against multi-drug resistant pathogens. In this study, the syntheses, characterization, photophysicochemical properties, and the applications of symmetrically and asymmetrically substituted cationic indium (III) porphyrins linked to silver/copper ferrite core-shell (Ag/CuFe2O4) magnetic nanoparticles (MNPs) as potential photosensitizers for PACT are reported. The synthesized complexes include axially modified porphyrins quaternized through an axial ligand. All the asymmetrically substituted porphyrins were linked to the NPs via an ester bond and the symmetrically substituted porphyrins were linked (peripherally and /or axially) via self-assembly (Ag-S and/or Ag-N). The impact of axial modification, peripheral substituents, conjugation to the NPs, the number of positive charges, and the chain length of the alkyl halides quaternizing agents on PACT efficacy and photophysicochemical properties of porphyrins were studied. High singlet oxygen quantum yields and antimicrobial log reductions were observed. Lipophilicity and hydrophilicity of the porphyrins were also studies, where the complexes quaternized with methyl iodide showed relatively high hydrophilicity character. Upon in vitro PACT studies, the quaternized complexes were observed to have 0% viable colony, signifying their effectiveness. Moreover, the highest log reductions of 9.27 were observed against S. aureus and 9.58 were observed against E. coli. The findings from this work delineate that singlet oxygen generation alone is not a distinct factor on the PACT efficacy of the porphyrin complexes, since some of the complexes have practically the same singlet oxygen quantum but different PACT activity. However, other contributing factors including water solubility play a significant role. , Thesis (MSc) -- Faculty of Science, Department of Chemistry, 2021
- Full Text:
- Date Issued: 2021-04
- Authors: Makola, Lekgowa Collen
- Date: 2021-04
- Subjects: Photochemotherapy , Photosensitizing compounds , Staphylococcus aureus , Escherichia coli , Indium , Porphyrins , Magnetic nanoparticles , Quaternize
- Language: English
- Type: thesis , text , Masters , MSc
- Identifier: http://hdl.handle.net/10962/177225 , vital:42801
- Description: Photodynamic antimicrobial chemotherapy (PACT) is a well-known antimicrobial therapy technique used against multi-drug resistant pathogens. In this study, the syntheses, characterization, photophysicochemical properties, and the applications of symmetrically and asymmetrically substituted cationic indium (III) porphyrins linked to silver/copper ferrite core-shell (Ag/CuFe2O4) magnetic nanoparticles (MNPs) as potential photosensitizers for PACT are reported. The synthesized complexes include axially modified porphyrins quaternized through an axial ligand. All the asymmetrically substituted porphyrins were linked to the NPs via an ester bond and the symmetrically substituted porphyrins were linked (peripherally and /or axially) via self-assembly (Ag-S and/or Ag-N). The impact of axial modification, peripheral substituents, conjugation to the NPs, the number of positive charges, and the chain length of the alkyl halides quaternizing agents on PACT efficacy and photophysicochemical properties of porphyrins were studied. High singlet oxygen quantum yields and antimicrobial log reductions were observed. Lipophilicity and hydrophilicity of the porphyrins were also studies, where the complexes quaternized with methyl iodide showed relatively high hydrophilicity character. Upon in vitro PACT studies, the quaternized complexes were observed to have 0% viable colony, signifying their effectiveness. Moreover, the highest log reductions of 9.27 were observed against S. aureus and 9.58 were observed against E. coli. The findings from this work delineate that singlet oxygen generation alone is not a distinct factor on the PACT efficacy of the porphyrin complexes, since some of the complexes have practically the same singlet oxygen quantum but different PACT activity. However, other contributing factors including water solubility play a significant role. , Thesis (MSc) -- Faculty of Science, Department of Chemistry, 2021
- Full Text:
- Date Issued: 2021-04
BODIPY and porphyrin dyes for direct glucose sensing and optical limiting applications
- Authors: Ndebele, Nobuhle
- Date: 2019
- Subjects: Boron compounds , Boric acid , Porphyrins , Dyes and dying -- Chemistry
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/97221 , vital:31412
- Description: A series of BODIPY dyes functionalised with boronic acid in the 3,5-positions were successfully synthesised and characterised by using various analytical techniques. The dyes were prepared through a slight modification of the conventional acid catalysed condensation method. Phenylboronic acid moieties were added as styryl groups at the 3,5-positions of the 1,3,5,7-tetrametylBODIPY cores using a modified Knoevengal condensation method. The addition of the styryls resulted in the main absorption band of the dyes red-shifting to the 630−650 nm region. The photophysical and electrochemical properties of these dyes were studied to determine whether the dyes are suitable for use in the fluorescent, colourimetric and electrochemical detection of glucose. Boronic acid moieties were added as bioreceptor recognition elements because they have an affinity for carbohydrates and therefore would be able to bind and “detect” glucose. The series of BODIPY dyes did not show a “turn-on” fluorescence effect upon addition with glucose at the physiological pH. This was attributed on the basis of molecular modelling to the absence of an MO localised on the boronic-acid-substituted styryl moieties that lie close in energy to the HOMO and LUMO that facilitates the formation of an intramolecular charge transfer state. However, colourimetric changes that are visible to the naked eye are observed at basic pH when glucose was added to the dye solutions. The dyes exhibited favourable electrochemical behaviour and were able to detect glucose directly in this context when glassy carbon electrodes are modified through the drop dry method. A series of Sn(IV) porphyrins with thienyl and phenyl groups at the meso-positions were successfully synthesised and characterised. Pyridine and tetrabutyl axial ligands were added to the porphyrins to limit aggregation. The optical limiting properties of these porphyrins and three styrylated BODIPY dyes were studied in benzene and dichloromethane. Dyes were also embedded in polystyrene and studied as thin films to further gauge their suitability for use in optical limiting applications. Second-order hyperpolarizability, third-order susceptibly, non-linear absorption with reversible saturable absorption and the optical limiting threshold, were the parameters studied. Three of the four porphyrins and the three styrylated BODIPY dyes showed favourable optical limiting behaviour, which was further enhanced when the dyes are embedded in polymer thin films.
- Full Text:
- Date Issued: 2019
- Authors: Ndebele, Nobuhle
- Date: 2019
- Subjects: Boron compounds , Boric acid , Porphyrins , Dyes and dying -- Chemistry
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/97221 , vital:31412
- Description: A series of BODIPY dyes functionalised with boronic acid in the 3,5-positions were successfully synthesised and characterised by using various analytical techniques. The dyes were prepared through a slight modification of the conventional acid catalysed condensation method. Phenylboronic acid moieties were added as styryl groups at the 3,5-positions of the 1,3,5,7-tetrametylBODIPY cores using a modified Knoevengal condensation method. The addition of the styryls resulted in the main absorption band of the dyes red-shifting to the 630−650 nm region. The photophysical and electrochemical properties of these dyes were studied to determine whether the dyes are suitable for use in the fluorescent, colourimetric and electrochemical detection of glucose. Boronic acid moieties were added as bioreceptor recognition elements because they have an affinity for carbohydrates and therefore would be able to bind and “detect” glucose. The series of BODIPY dyes did not show a “turn-on” fluorescence effect upon addition with glucose at the physiological pH. This was attributed on the basis of molecular modelling to the absence of an MO localised on the boronic-acid-substituted styryl moieties that lie close in energy to the HOMO and LUMO that facilitates the formation of an intramolecular charge transfer state. However, colourimetric changes that are visible to the naked eye are observed at basic pH when glucose was added to the dye solutions. The dyes exhibited favourable electrochemical behaviour and were able to detect glucose directly in this context when glassy carbon electrodes are modified through the drop dry method. A series of Sn(IV) porphyrins with thienyl and phenyl groups at the meso-positions were successfully synthesised and characterised. Pyridine and tetrabutyl axial ligands were added to the porphyrins to limit aggregation. The optical limiting properties of these porphyrins and three styrylated BODIPY dyes were studied in benzene and dichloromethane. Dyes were also embedded in polystyrene and studied as thin films to further gauge their suitability for use in optical limiting applications. Second-order hyperpolarizability, third-order susceptibly, non-linear absorption with reversible saturable absorption and the optical limiting threshold, were the parameters studied. Three of the four porphyrins and the three styrylated BODIPY dyes showed favourable optical limiting behaviour, which was further enhanced when the dyes are embedded in polymer thin films.
- Full Text:
- Date Issued: 2019
Photocatalysis of 4-chloro and 4-nonylphenols using novel symmetric phthalocyanines and asymmetric porphyrin supported on polyacrylonitrite nanofibres
- Authors: Jones, Benjamin Martin
- Date: 2020
- Subjects: Nanoparticles , Phthalocyanines , Electrospinning , Porphyrins , Nanofibers , Photocatalysis , Photocatalysis -- Environmental aspects
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/164770 , vital:41163
- Description: This work explores the synthesis and characterisation of novel symmetrical phthalocyanines and novel asymmetric porphyrins that have been embedded or linked respectively,and electrospun into fibres for application in the photocatalysis of environmental pollutants. The phthalocyanines contain pyrrole moieties without hetero atom linkers to maintain a rigid structure. The porphyrin contains a carboxy moiety utilized to construct an amide bond between the complex and the polymer prior to the spinning process. The new compounds were characterized by elemental analyses, proton nuclear magnetic resonance (HNMR)Fourier-transform infrared spectroscopy (FTIR), MALDI-TOF and UV-vis spectroscopy. The general trends of fluorescence, triplet and singlet oxygen quantum yields are described as well as their appropriate lifetimes. The photocatalytic activity of phthalocyanine embedded fibres were compared against those that had been dyed. Unfortunately, during the degradation process, the dyed fibres leeched compound and the studies could not be continued. It was seen that the porphyrin fibres linked to the polymer showed the most efficient photocatalytic activity against 4-cholorphenol and 4-nonylphenol due to irradiation at lower wavelengths consequently having higher frequencies and transferring more energy.
- Full Text:
- Date Issued: 2020
- Authors: Jones, Benjamin Martin
- Date: 2020
- Subjects: Nanoparticles , Phthalocyanines , Electrospinning , Porphyrins , Nanofibers , Photocatalysis , Photocatalysis -- Environmental aspects
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/164770 , vital:41163
- Description: This work explores the synthesis and characterisation of novel symmetrical phthalocyanines and novel asymmetric porphyrins that have been embedded or linked respectively,and electrospun into fibres for application in the photocatalysis of environmental pollutants. The phthalocyanines contain pyrrole moieties without hetero atom linkers to maintain a rigid structure. The porphyrin contains a carboxy moiety utilized to construct an amide bond between the complex and the polymer prior to the spinning process. The new compounds were characterized by elemental analyses, proton nuclear magnetic resonance (HNMR)Fourier-transform infrared spectroscopy (FTIR), MALDI-TOF and UV-vis spectroscopy. The general trends of fluorescence, triplet and singlet oxygen quantum yields are described as well as their appropriate lifetimes. The photocatalytic activity of phthalocyanine embedded fibres were compared against those that had been dyed. Unfortunately, during the degradation process, the dyed fibres leeched compound and the studies could not be continued. It was seen that the porphyrin fibres linked to the polymer showed the most efficient photocatalytic activity against 4-cholorphenol and 4-nonylphenol due to irradiation at lower wavelengths consequently having higher frequencies and transferring more energy.
- Full Text:
- Date Issued: 2020
Photophysical properties and photodynamic therapy activities of symmetrical and asymmetrical porphyrins embedded into Pluronic polymer micelles and nonlinear optical properties of an asymmetrical phthalocyanine
- Authors: Managa, Muthumuni Elizabeth
- Date: 2019
- Subjects: Porphyrins , Phthalocyanines
- Language: English
- Type: text , Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/67625 , vital:29122
- Description: This work reports on the synthesis of symmetrical and asymmetrical novel porphyrins that have been incorporated into Pluronic polymers, as well as the synthesis of asymmetrical phthalocyanine. The new compounds were characterized by elemental analysis, Fourier-transform infrared spectroscopy (FT-IR), proton nuclear magnetic resonance (1H NMR), mass spectrometry and UV–Visible spectroscopy. The porphyrins that are synthesised were not water soluble but upon incorporating into Pluronic polymer micelles, they became water soluble. The polymer was also modified and linked to folic acid, to enhance selectivity for photodynamic therapy application, where MCF7 breast cancer cells were used. The singlet oxygen quantum yields were lower for the metal free porphyrins as compared to metalled ones due to the heavy atom effect of ClGa, Zn and Cl2Si in the latter which encourages intersystem crossing to the triplet state. Singlet oxygen quantum yields for water soluble derivatives increased upon being encapsulated into the micelles for all. The Stern-Volmer constant (Ksv), binding constant (Kb) and number of binding sites (n) were investigated in order to understand the interaction between the polymer micelles and the porphyrins, and it was showed that the central metals play a role in the manner which the porphyrin interacts with the micelles. The dark toxicity and photodynamic activity of the novel porphyrins upon encapsulating to Pluronic polymer micelles is also reported. There was minimal dark toxicity for all complexes with > 90% cell survival. The photodynamic activity of water insoluble porphyrins improved when encapsulated into the micelles. Novel asymmetrical phthalocyanines were also synthesised for nonlinear optics (NLO) studies in solution and thin films.
- Full Text:
- Date Issued: 2019
- Authors: Managa, Muthumuni Elizabeth
- Date: 2019
- Subjects: Porphyrins , Phthalocyanines
- Language: English
- Type: text , Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/67625 , vital:29122
- Description: This work reports on the synthesis of symmetrical and asymmetrical novel porphyrins that have been incorporated into Pluronic polymers, as well as the synthesis of asymmetrical phthalocyanine. The new compounds were characterized by elemental analysis, Fourier-transform infrared spectroscopy (FT-IR), proton nuclear magnetic resonance (1H NMR), mass spectrometry and UV–Visible spectroscopy. The porphyrins that are synthesised were not water soluble but upon incorporating into Pluronic polymer micelles, they became water soluble. The polymer was also modified and linked to folic acid, to enhance selectivity for photodynamic therapy application, where MCF7 breast cancer cells were used. The singlet oxygen quantum yields were lower for the metal free porphyrins as compared to metalled ones due to the heavy atom effect of ClGa, Zn and Cl2Si in the latter which encourages intersystem crossing to the triplet state. Singlet oxygen quantum yields for water soluble derivatives increased upon being encapsulated into the micelles for all. The Stern-Volmer constant (Ksv), binding constant (Kb) and number of binding sites (n) were investigated in order to understand the interaction between the polymer micelles and the porphyrins, and it was showed that the central metals play a role in the manner which the porphyrin interacts with the micelles. The dark toxicity and photodynamic activity of the novel porphyrins upon encapsulating to Pluronic polymer micelles is also reported. There was minimal dark toxicity for all complexes with > 90% cell survival. The photodynamic activity of water insoluble porphyrins improved when encapsulated into the micelles. Novel asymmetrical phthalocyanines were also synthesised for nonlinear optics (NLO) studies in solution and thin films.
- Full Text:
- Date Issued: 2019
Evaluation of metallophthalocyanine functionalized photocatalytic asymmetric polymer membranes for pollution control and antimicrobial activity
- Mafukidze, Donovan Musizvinoda Chidyamurimi
- Authors: Mafukidze, Donovan Musizvinoda Chidyamurimi
- Date: 2021
- Subjects: Photosensitizing compounds , Water -- Purification -- Photocatalysis , Phthalocyanines , Polymeric membranes , Porphyrins
- Language: English
- Type: text , Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/171357 , vital:42052 , 10.21504/10962/171357
- Description: The conceptualisation of photosensitizing water treatment polymer membranes using phthalocyanine based photosensitizers is reported in this thesis. The key to successful preparation of stable photoactive polymer membranes was established as the covalent anchorage of the photosensitizer to a polymer, which was proven by singlet oxygen generation by the membranes without photosensitizer deterioration. Despite this limitation, the covalent linkage-incapable unsubstituted zinc (II) phthalocyanine (complex 2) was applied as a nanoconjugate of graphene quantum dots (2π(GQDs)). 2π(GQDs) was formed through π-π stacking, and was then covalently anchored, as a proof of concept. This concept was also applied to 2-(4-carboxyphenoxy) phthalocyaninato zinc (II) (complex 3) which is capable of covalent linkage but proved to deteriorate the efficiency of singlet oxygen formation with comparison to the covalent conjugates. Singlet oxygen generation by functionalized polymer membranes rendered them photocatalytic in the degradation of organic pollutants and microorganisms in water. Organic pollutant degradation capability was exemplified by 2π(GQDs) and a porphyrin-phthalocyanine heterodyad (complex 10) functionalized membranes (2π(GQDs)-memb and 10-memb respectively), where a MPc loading of approximately 0.139 μmol MPc/g of membrane was able to achieve a 4-chlorophenol degradation rate of 3.77 × 10−6 mol L−1 min−1 in a second order reaction with an initial 4-chlorophenol concentration of 3.24 × 10−4 mol L−1 for 2π(GQDs)-memb as an example. Antibacterial studies against S.aureus using a quaternized MPc and conjugates of silver triangular nanoprisms with zinc (II) and indium (III) MPcs showed note-worthy improvements in photodynamic antimicrobial chemotherapy (PACT) activity in comparison to the unquaternized MPc precursor, and the free zinc and indium MPcs respectively. Functionalization of polymer membranes with these higher activity photosensitizers translated to the formation of potentially superior biological fouling resistant membranes. The use of porphyrin-phthalocyanine polynuclei arrays (complex 10) in polymer membrane functionalization resulted in the use of a wider wavelength range (white light). The findings from this work as a whole, thus presents the potential applicability of phthalocyanine functionalized polymer membranes in water treatment technology.
- Full Text:
- Date Issued: 2021
- Authors: Mafukidze, Donovan Musizvinoda Chidyamurimi
- Date: 2021
- Subjects: Photosensitizing compounds , Water -- Purification -- Photocatalysis , Phthalocyanines , Polymeric membranes , Porphyrins
- Language: English
- Type: text , Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/171357 , vital:42052 , 10.21504/10962/171357
- Description: The conceptualisation of photosensitizing water treatment polymer membranes using phthalocyanine based photosensitizers is reported in this thesis. The key to successful preparation of stable photoactive polymer membranes was established as the covalent anchorage of the photosensitizer to a polymer, which was proven by singlet oxygen generation by the membranes without photosensitizer deterioration. Despite this limitation, the covalent linkage-incapable unsubstituted zinc (II) phthalocyanine (complex 2) was applied as a nanoconjugate of graphene quantum dots (2π(GQDs)). 2π(GQDs) was formed through π-π stacking, and was then covalently anchored, as a proof of concept. This concept was also applied to 2-(4-carboxyphenoxy) phthalocyaninato zinc (II) (complex 3) which is capable of covalent linkage but proved to deteriorate the efficiency of singlet oxygen formation with comparison to the covalent conjugates. Singlet oxygen generation by functionalized polymer membranes rendered them photocatalytic in the degradation of organic pollutants and microorganisms in water. Organic pollutant degradation capability was exemplified by 2π(GQDs) and a porphyrin-phthalocyanine heterodyad (complex 10) functionalized membranes (2π(GQDs)-memb and 10-memb respectively), where a MPc loading of approximately 0.139 μmol MPc/g of membrane was able to achieve a 4-chlorophenol degradation rate of 3.77 × 10−6 mol L−1 min−1 in a second order reaction with an initial 4-chlorophenol concentration of 3.24 × 10−4 mol L−1 for 2π(GQDs)-memb as an example. Antibacterial studies against S.aureus using a quaternized MPc and conjugates of silver triangular nanoprisms with zinc (II) and indium (III) MPcs showed note-worthy improvements in photodynamic antimicrobial chemotherapy (PACT) activity in comparison to the unquaternized MPc precursor, and the free zinc and indium MPcs respectively. Functionalization of polymer membranes with these higher activity photosensitizers translated to the formation of potentially superior biological fouling resistant membranes. The use of porphyrin-phthalocyanine polynuclei arrays (complex 10) in polymer membrane functionalization resulted in the use of a wider wavelength range (white light). The findings from this work as a whole, thus presents the potential applicability of phthalocyanine functionalized polymer membranes in water treatment technology.
- Full Text:
- Date Issued: 2021
Photodynamic anticancer and antimicrobial activities of π-extended BODIPY dyes and cationic mitochondria-targeted porphyrins
- Authors: Chiyumba, Choonzo Nachoobe
- Date: 2022-10-14
- Subjects: Dyes and dyeing Chemistry , Mitochondria , Cancer Chemotherapy , Porphyrins , Molecules Models , Photochemotherapy
- Language: English
- Type: Academic theses , Master's theses , text
- Identifier: http://hdl.handle.net/10962/362785 , vital:65362
- Description: Cancer is among the most devastating diseases and is mainly caused by gene mutation. This could be hereditary, or the mutation could be stimulated due to a lifestyle one lives, such as smoking, which induces lung cancer. The high morbidity rates of cancer are attributed to it being metastatic. The relatively poor physicochemical properties of existing drugs have caused treatment to be ineffective. Photofrin®, Foscan®, and Photogem® are some of the porphyrin-based derivatives approved by the Food and Drug Administration (FDA) for use in photodynamic therapy (PDT). Despite having such drugs, the quest to find better cancer drugs is still ongoing and 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) dyes are among the molecules that are being studied as potential photosensitisers (PS) in PDT. However, these molecules suffer from poor solubility and ineffective generation of singlet oxygen, the main ingredient in PDT treatment. Furthermore, photosensitisers used in PDT face a problem with hypoxic conditions associated with cancer cells, which causes the generation of singlet oxygen to be relatively low. The PS also suffer from the untargeted treatment, increasing their toxicity. Therefore, the main aim of this study was to improve the bioavailability of BODIPY dyes. Thus, a series of BODPIY dyes were synthesised with hydrogen bond accepting atoms and heavy atoms that enhance singlet oxygen generation. Additionally, to override hypoxia conditions, porphyrins with mitochondria targeting properties were synthesised since it has been well established that the mitochondria will always have a decent amount of oxygen in cancerous cells. When employed as PS in PDT studies, these molecules have better cytotoxic abilities than BODIPY dyes, and this potency was credited to their mitochondria targeting ability and efficient singlet oxygen generation. Finally, this study reports the synthesis of di- and mono-substituted BODIPY dyes with improved solubility and porphyrins substituted with triphenyl phosphine, a mitochondria targeting moiety. On the other hand, the work further illustrates the synthesis of β-substituted cationic porphyrin with mitochondria targeting properties. , Thesis (MSc) -- Faculty of Science, Chemistry, 2022
- Full Text:
- Date Issued: 2022-10-14
- Authors: Chiyumba, Choonzo Nachoobe
- Date: 2022-10-14
- Subjects: Dyes and dyeing Chemistry , Mitochondria , Cancer Chemotherapy , Porphyrins , Molecules Models , Photochemotherapy
- Language: English
- Type: Academic theses , Master's theses , text
- Identifier: http://hdl.handle.net/10962/362785 , vital:65362
- Description: Cancer is among the most devastating diseases and is mainly caused by gene mutation. This could be hereditary, or the mutation could be stimulated due to a lifestyle one lives, such as smoking, which induces lung cancer. The high morbidity rates of cancer are attributed to it being metastatic. The relatively poor physicochemical properties of existing drugs have caused treatment to be ineffective. Photofrin®, Foscan®, and Photogem® are some of the porphyrin-based derivatives approved by the Food and Drug Administration (FDA) for use in photodynamic therapy (PDT). Despite having such drugs, the quest to find better cancer drugs is still ongoing and 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) dyes are among the molecules that are being studied as potential photosensitisers (PS) in PDT. However, these molecules suffer from poor solubility and ineffective generation of singlet oxygen, the main ingredient in PDT treatment. Furthermore, photosensitisers used in PDT face a problem with hypoxic conditions associated with cancer cells, which causes the generation of singlet oxygen to be relatively low. The PS also suffer from the untargeted treatment, increasing their toxicity. Therefore, the main aim of this study was to improve the bioavailability of BODIPY dyes. Thus, a series of BODPIY dyes were synthesised with hydrogen bond accepting atoms and heavy atoms that enhance singlet oxygen generation. Additionally, to override hypoxia conditions, porphyrins with mitochondria targeting properties were synthesised since it has been well established that the mitochondria will always have a decent amount of oxygen in cancerous cells. When employed as PS in PDT studies, these molecules have better cytotoxic abilities than BODIPY dyes, and this potency was credited to their mitochondria targeting ability and efficient singlet oxygen generation. Finally, this study reports the synthesis of di- and mono-substituted BODIPY dyes with improved solubility and porphyrins substituted with triphenyl phosphine, a mitochondria targeting moiety. On the other hand, the work further illustrates the synthesis of β-substituted cationic porphyrin with mitochondria targeting properties. , Thesis (MSc) -- Faculty of Science, Chemistry, 2022
- Full Text:
- Date Issued: 2022-10-14
The synthesis and characterisation of Sn(IV) porphyrin derivatives and their potential application in anti-cancer and antimicrobial photodynamic therapy
- Authors: Dingiswayo, Somila
- Date: 2021-10
- Subjects: Porphyrins , Photochemotherapy , Cancer Photochemotherapy , Active oxygen Physiological effect , Aromaticity (Chemistry) , Tetrapyrroles , Magnetic circular dichroism , Corroles , Chlorins , Photodynamic antimicrobial chemotherapy (PACT)
- Language: English
- Type: Masters theses , text
- Identifier: http://hdl.handle.net/10962/188843 , vital:44791
- Description: In photodynamic therapy (PDT), the activation of light-sensitive drugs in tumour cells produces reactive singlet oxygen species, which cause tumour destruction through a cascade of biochemical reactions. Over the years, the wavelength of activation has been shown to be a critical factor in the penetration of light. Hence the properties of photosensitiser dyes in this context shape their ability to treat deep-seated tumours. In this study, the synthesis, structural characterisation and photophysicochemical properties of a series of Sn(IV) porphyrins with meso-methylthiophenyl rings that have been prepared to study their PDT and photodynamic antimicrobial chemotherapy (PACT) activity properties are reported. The series of Sn(IV) complexes is comprised of a porphyrin (1-Sn), a corrole (2-Sn), a chlorin (3-Sn) and an N-confused porphyrin (4-Sn). Herein, the low symmetry Sn(IV) porphyrin derivatives are shown to have excellent singlet oxygen generation capabilities, and lifetimes of the triplet excited states were in the microsecond range. For example, 4-Sn had a singlet oxygen quantum yield (ФΔ) and an excited triplet state lifetime (τT) of 0.88 and 27 μs, respectively. The complexes were studied using UV-visible and magnetic circular dichroism (MCD) spectroscopies. Interestingly, the positive-to-negative sign sequences of the Faraday B0 terms of 2-Sn and 3-Sn reveal that the structural modifications involved break the degeneracy of the MOs derived from the 1eg* LUMO of the porphyrin 1-Sn. In contrast, a conventional negative-to-positive sign sequence is observed for 4-Sn, since the confusion of a pyrrole moiety also results in a large separation of the 1a1u and 1a2u MOs of the porphyrin 1-Sn that are derived from the HOMO of a C16H162−parent hydrocarbon perimeter. The trends in the electronic structures of the Sn(IV) complexes were further investigated through a series of time-dependent density functional theory calculations, so that the suitability of the different types of complex for use in singlet oxygen applications could be further explored. During in vitro photodynamic antimicrobial chemotherapy (PACT) studies, chlorin derivative 3-Sn had the highest activity towards S. aureus and E. coli with log10 reductions of 10.5 and 8.74, respectively. The unusually high activity of 3-Sn against E.coli suggests that the interaction of neutral photosensitisers with gram-negativebacteria is more complex than previously understood. Anti-cancer PDT studies demonstrated that the photosensitisers had negligible dark cytotoxicity. Upon photoirradiation, the Sn(IV) complexes consistently exhibited IC50 values lower than 15 μM against MCF-7 adenocarcinoma cells. An IC50 value of 1.4 μM for 4-Sn after activation at the deep-red region of the spectrum demonstrates that complexes of this type merit further in-depth investigation. The results provide evidence that the low-symmetry Sn(IV) chlorins and N-confused porphyrins merit further in-depth study for use in singlet oxygen applications. , Thesis (MSc) -- Faculty of Science, Chemistry, 2021
- Full Text:
- Date Issued: 2021-10
- Authors: Dingiswayo, Somila
- Date: 2021-10
- Subjects: Porphyrins , Photochemotherapy , Cancer Photochemotherapy , Active oxygen Physiological effect , Aromaticity (Chemistry) , Tetrapyrroles , Magnetic circular dichroism , Corroles , Chlorins , Photodynamic antimicrobial chemotherapy (PACT)
- Language: English
- Type: Masters theses , text
- Identifier: http://hdl.handle.net/10962/188843 , vital:44791
- Description: In photodynamic therapy (PDT), the activation of light-sensitive drugs in tumour cells produces reactive singlet oxygen species, which cause tumour destruction through a cascade of biochemical reactions. Over the years, the wavelength of activation has been shown to be a critical factor in the penetration of light. Hence the properties of photosensitiser dyes in this context shape their ability to treat deep-seated tumours. In this study, the synthesis, structural characterisation and photophysicochemical properties of a series of Sn(IV) porphyrins with meso-methylthiophenyl rings that have been prepared to study their PDT and photodynamic antimicrobial chemotherapy (PACT) activity properties are reported. The series of Sn(IV) complexes is comprised of a porphyrin (1-Sn), a corrole (2-Sn), a chlorin (3-Sn) and an N-confused porphyrin (4-Sn). Herein, the low symmetry Sn(IV) porphyrin derivatives are shown to have excellent singlet oxygen generation capabilities, and lifetimes of the triplet excited states were in the microsecond range. For example, 4-Sn had a singlet oxygen quantum yield (ФΔ) and an excited triplet state lifetime (τT) of 0.88 and 27 μs, respectively. The complexes were studied using UV-visible and magnetic circular dichroism (MCD) spectroscopies. Interestingly, the positive-to-negative sign sequences of the Faraday B0 terms of 2-Sn and 3-Sn reveal that the structural modifications involved break the degeneracy of the MOs derived from the 1eg* LUMO of the porphyrin 1-Sn. In contrast, a conventional negative-to-positive sign sequence is observed for 4-Sn, since the confusion of a pyrrole moiety also results in a large separation of the 1a1u and 1a2u MOs of the porphyrin 1-Sn that are derived from the HOMO of a C16H162−parent hydrocarbon perimeter. The trends in the electronic structures of the Sn(IV) complexes were further investigated through a series of time-dependent density functional theory calculations, so that the suitability of the different types of complex for use in singlet oxygen applications could be further explored. During in vitro photodynamic antimicrobial chemotherapy (PACT) studies, chlorin derivative 3-Sn had the highest activity towards S. aureus and E. coli with log10 reductions of 10.5 and 8.74, respectively. The unusually high activity of 3-Sn against E.coli suggests that the interaction of neutral photosensitisers with gram-negativebacteria is more complex than previously understood. Anti-cancer PDT studies demonstrated that the photosensitisers had negligible dark cytotoxicity. Upon photoirradiation, the Sn(IV) complexes consistently exhibited IC50 values lower than 15 μM against MCF-7 adenocarcinoma cells. An IC50 value of 1.4 μM for 4-Sn after activation at the deep-red region of the spectrum demonstrates that complexes of this type merit further in-depth investigation. The results provide evidence that the low-symmetry Sn(IV) chlorins and N-confused porphyrins merit further in-depth study for use in singlet oxygen applications. , Thesis (MSc) -- Faculty of Science, Chemistry, 2021
- Full Text:
- Date Issued: 2021-10
In vitro susceptibility of Staphylococcus aureus to porphyrin-silver mediated photodynamic antimicrobial chemotherapy
- Authors: Shabangu, Samuel Malewa
- Date: 2020
- Subjects: Porphyrins , Nanoparticles , Photochemotherapy , Drug resistance in microorganisms , Staphylococcus aureus
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/167476 , vital:41484
- Description: This work reports on the syntheses and characterization of symmetrical and unsymmetrical porphyrin complexes namely, 5,10,15,20-tetra(4-pyridyl)-porphyrinato zinc(II) (1), 5,10,15,20-tetrathienyl porphyrinato zinc(II) (2), 5-(4-hydroxyphenyl)-10, 15, 20-tris(2-thienyl) porphyrinato zinc(II) (3), 5-(4-carboxyphenyl)-10,15,20-tris(pentafluorophenyl)- porphyrinato zinc(II) (4), 5-(4-carboxyphenyl)-10,15,20-triphenyl-porphyrinato zinc(II) (5) and 5-(4-carboxyphenyl)-10, 15, 20-tris(2-thienyl)-porphyrinato zinc(II) (6). The synthesis of silver nanoparticles (AgNPs) was also undertaken in this research work. Complexes 1, 2, 3 and 6 were linked to oleic acid/oleylamine functionalized nanoparticles via self-assembly and 4-6 were linked via covalent interaction through an amide bond to glutathione capped AgNPs. The effect of nature of bond along with symmetry were investigated, of interest were the five membered thienyl substituents. The photophysical and photochemical behaviour of the complexes and their conjugates with AgNPs were investigated in dimethylformamide. The porphyrin and AgNPs conjugates afforded an increase in singlet oxygen quantum yield. Complexes 1-6 and their conjugates were used for photodynamic antimicrobial chemotherapy of Staphylococcus aureus. The antimicrobial studies were done in two different concentrations of 0.36 and 2.0 μg/mL. The thienyl substituted porphyrin complexes and their conjugates gave better photodynamic activity as compared to phenyl analogues
- Full Text:
- Date Issued: 2020
- Authors: Shabangu, Samuel Malewa
- Date: 2020
- Subjects: Porphyrins , Nanoparticles , Photochemotherapy , Drug resistance in microorganisms , Staphylococcus aureus
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/167476 , vital:41484
- Description: This work reports on the syntheses and characterization of symmetrical and unsymmetrical porphyrin complexes namely, 5,10,15,20-tetra(4-pyridyl)-porphyrinato zinc(II) (1), 5,10,15,20-tetrathienyl porphyrinato zinc(II) (2), 5-(4-hydroxyphenyl)-10, 15, 20-tris(2-thienyl) porphyrinato zinc(II) (3), 5-(4-carboxyphenyl)-10,15,20-tris(pentafluorophenyl)- porphyrinato zinc(II) (4), 5-(4-carboxyphenyl)-10,15,20-triphenyl-porphyrinato zinc(II) (5) and 5-(4-carboxyphenyl)-10, 15, 20-tris(2-thienyl)-porphyrinato zinc(II) (6). The synthesis of silver nanoparticles (AgNPs) was also undertaken in this research work. Complexes 1, 2, 3 and 6 were linked to oleic acid/oleylamine functionalized nanoparticles via self-assembly and 4-6 were linked via covalent interaction through an amide bond to glutathione capped AgNPs. The effect of nature of bond along with symmetry were investigated, of interest were the five membered thienyl substituents. The photophysical and photochemical behaviour of the complexes and their conjugates with AgNPs were investigated in dimethylformamide. The porphyrin and AgNPs conjugates afforded an increase in singlet oxygen quantum yield. Complexes 1-6 and their conjugates were used for photodynamic antimicrobial chemotherapy of Staphylococcus aureus. The antimicrobial studies were done in two different concentrations of 0.36 and 2.0 μg/mL. The thienyl substituted porphyrin complexes and their conjugates gave better photodynamic activity as compared to phenyl analogues
- Full Text:
- Date Issued: 2020
Photodynamic antimicrobial chemotherapy activities of porphyrin- and phthalocyanine-platinum nanoparticle conjugates
- Authors: Managa, Muthumuni Elizabeth
- Date: 2015
- Subjects: Photochemotherapy , Anti-infective agents , Porphyrins , Phthalocyanines , Platinum , Nanoparticles , Bioconjugates , Electrospinning
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:4539 , http://hdl.handle.net/10962/d1017919
- Description: This work reports on the conjugation of differently shaped Pt nanoparticles (PtNPs) with ClGa(III) 5,10,15,20-tetrakis-(4-carboxyphenyl) porphyrin (1) as well as chloro - (5,10,15,20-tetrakis (4- (4- carboxy phenycarbonoimidoyl) phenyl) porphyrinato) gallium(III) (2) The work also reports on platination of dihydroxosilicon octacarboxyphthalocyanine (OH)₂SiOCPc (3) to give dihydroxosilicontris(diaquaplatinum)octacarboxyphthalocyanine (OH)₂SiOCPc(Pt)₃ (4). The resulting conjugates were used for photodynamic antimicrobial chemotherapy against S. aureus, E. coli and C. albicans. The degree of photo-inactivation is dependent on concentration of the conjugates, light dose (fluence) and illumination time. The log reduction obtained for 1 when conjugated to cubic PtNPs was 4.64 log (which indicate 99.99 percent of the bacteria have been killed), which is much higher than 3.94 log unit for 1-hexagonal PtNPs and 3.31 log units for 1-unshaped PtNPs. Complex 2 conjugated to hexagonal PtNPs showed 18 nm red shift in the Soret band when compared to 2 alone. Complex 2 and 2-hexagonal PtNPs as well showed promising photodynamic antimicrobial chemotherapy (PACT) activity against S. aureus, E. coli and C. albicans in solution where the log reduction obtained was 4.92, 3.76, and 3.95 respectively for 2-hexagonal PtNPs. The singlet oxygen quantum yields obtained were higher at 0.56 for 2-hexagonl PtNPs in DMF while that of 2 was 0.52 in the same solvent. This resulted in improved PACT activity for 2-hexagonal PtNPs compared to 2. Complex 4 showed slight blue shifting of the absorption spectrum when compared to complex 3 The antimicrobial activity of 4 were promising as the highest log reduction value was observed when compared to the porphyrin conjugates.
- Full Text:
- Date Issued: 2015
- Authors: Managa, Muthumuni Elizabeth
- Date: 2015
- Subjects: Photochemotherapy , Anti-infective agents , Porphyrins , Phthalocyanines , Platinum , Nanoparticles , Bioconjugates , Electrospinning
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:4539 , http://hdl.handle.net/10962/d1017919
- Description: This work reports on the conjugation of differently shaped Pt nanoparticles (PtNPs) with ClGa(III) 5,10,15,20-tetrakis-(4-carboxyphenyl) porphyrin (1) as well as chloro - (5,10,15,20-tetrakis (4- (4- carboxy phenycarbonoimidoyl) phenyl) porphyrinato) gallium(III) (2) The work also reports on platination of dihydroxosilicon octacarboxyphthalocyanine (OH)₂SiOCPc (3) to give dihydroxosilicontris(diaquaplatinum)octacarboxyphthalocyanine (OH)₂SiOCPc(Pt)₃ (4). The resulting conjugates were used for photodynamic antimicrobial chemotherapy against S. aureus, E. coli and C. albicans. The degree of photo-inactivation is dependent on concentration of the conjugates, light dose (fluence) and illumination time. The log reduction obtained for 1 when conjugated to cubic PtNPs was 4.64 log (which indicate 99.99 percent of the bacteria have been killed), which is much higher than 3.94 log unit for 1-hexagonal PtNPs and 3.31 log units for 1-unshaped PtNPs. Complex 2 conjugated to hexagonal PtNPs showed 18 nm red shift in the Soret band when compared to 2 alone. Complex 2 and 2-hexagonal PtNPs as well showed promising photodynamic antimicrobial chemotherapy (PACT) activity against S. aureus, E. coli and C. albicans in solution where the log reduction obtained was 4.92, 3.76, and 3.95 respectively for 2-hexagonal PtNPs. The singlet oxygen quantum yields obtained were higher at 0.56 for 2-hexagonl PtNPs in DMF while that of 2 was 0.52 in the same solvent. This resulted in improved PACT activity for 2-hexagonal PtNPs compared to 2. Complex 4 showed slight blue shifting of the absorption spectrum when compared to complex 3 The antimicrobial activity of 4 were promising as the highest log reduction value was observed when compared to the porphyrin conjugates.
- Full Text:
- Date Issued: 2015
The photodynamic therapeutic activities and optical limiting properties of metalated asymmetric porphyrins and corroles
- Authors: Burgess, Kristen Paige
- Date: 2023-10-13
- Subjects: Porphyrins , Corrole , Photochemotherapy , Anti-infective agents , Nonlinear optics , Z-scan technique , Active oxygen , Time-dependent density functional theory , Chemical synthesis
- Language: English
- Type: Academic theses , Master's theses , text
- Identifier: http://hdl.handle.net/10962/424490 , vital:72158
- Description: Cancer is a devastating disease that is a leading cause of death worldwide. Despite the available cancer treatments, there is a significant need to improve the therapeutic approach towards this disease. Photodynamic therapy (PDT) is an alternative approach for treating cancer, which requires a photosensitiser, molecular oxygen and light. Although some porphyrin-based derivatives have been approved by the United States Food and Drug Administration (FDA) and other similar agencies elsewhere for photodynamic therapy, their relatively poor photophysicochemical properties mean that there is an ongoing need for new photosensitiser dyes. Singlet oxygen photosensitiser dyes can also be used to treat bacteria that develop antimicrobial resistance in the context of photodynamic antimicrobial chemotherapy (PACT). The main aim of this study was to synthesise and characterise a series of porphyrin dyes with 4-quinolinyl, thien-2-yl and 4-bromo-thien-2-yl meso-aryl groups and their Sn(IV) and In(III) complexes, as well as their corrole analogues. Corroles are contracted macrocycles that have interesting optical properties. The corroles selected for study were found to be difficult to synthesise and purify and had unfavourable photophysicochemical properties and were thus omitted from the PDT and PACT biological applications within this thesis. High- and low-symmetry A4 and ABAB type meso-tetraarylporphyrins porphyrins were synthesised to improve the photophysicochemical properties of the photosensitisers; the utility of these dyes as photosensitisers was studied against the MCF-7 breast cancer cell line for PDT and against Staphylococcus aureus and Escherichia coli for PACT. The thienyl-2-yl rings were introduced to red shift the lowest energy Q band towards the phototherapeutic window, while quaternisation of the nitrogen and sulfur atoms of the 4-quinolinyl and thien-2-yl rings to introduce a cationic nature was explored to improve the bioavailability of the drugs and uptake into the target cell walls for improved efficacy. Heavy Sn(IV) and In(III) central metal ions were introduced to enhance the singlet oxygen quantum yields and limit aggregation through axial ligation. The bromine atoms of the 4-bromo-thien-2-yl meso-aryl rings were also introduced to enhance the singlet oxygen quantum yields of the dyes. Furthermore, the utility of the porphyrin and corrole molecules for optical limiting properties to limit laser radiation to protect optical devices, including eyes, was explored by the z-scan technique. One of the dyes studied, Sn(IV) tetrathien-2-ylporphyrin, that exhibited the most favourable reverse saturable absorbance (RSA) response was embedded into a poly(bisphenol carbonate A) polymer thin film to further explore its suitability for practical applications. , Thesis (MSc) -- Faculty of Science, Chemistry, 2023
- Full Text:
- Date Issued: 2023-10-13
- Authors: Burgess, Kristen Paige
- Date: 2023-10-13
- Subjects: Porphyrins , Corrole , Photochemotherapy , Anti-infective agents , Nonlinear optics , Z-scan technique , Active oxygen , Time-dependent density functional theory , Chemical synthesis
- Language: English
- Type: Academic theses , Master's theses , text
- Identifier: http://hdl.handle.net/10962/424490 , vital:72158
- Description: Cancer is a devastating disease that is a leading cause of death worldwide. Despite the available cancer treatments, there is a significant need to improve the therapeutic approach towards this disease. Photodynamic therapy (PDT) is an alternative approach for treating cancer, which requires a photosensitiser, molecular oxygen and light. Although some porphyrin-based derivatives have been approved by the United States Food and Drug Administration (FDA) and other similar agencies elsewhere for photodynamic therapy, their relatively poor photophysicochemical properties mean that there is an ongoing need for new photosensitiser dyes. Singlet oxygen photosensitiser dyes can also be used to treat bacteria that develop antimicrobial resistance in the context of photodynamic antimicrobial chemotherapy (PACT). The main aim of this study was to synthesise and characterise a series of porphyrin dyes with 4-quinolinyl, thien-2-yl and 4-bromo-thien-2-yl meso-aryl groups and their Sn(IV) and In(III) complexes, as well as their corrole analogues. Corroles are contracted macrocycles that have interesting optical properties. The corroles selected for study were found to be difficult to synthesise and purify and had unfavourable photophysicochemical properties and were thus omitted from the PDT and PACT biological applications within this thesis. High- and low-symmetry A4 and ABAB type meso-tetraarylporphyrins porphyrins were synthesised to improve the photophysicochemical properties of the photosensitisers; the utility of these dyes as photosensitisers was studied against the MCF-7 breast cancer cell line for PDT and against Staphylococcus aureus and Escherichia coli for PACT. The thienyl-2-yl rings were introduced to red shift the lowest energy Q band towards the phototherapeutic window, while quaternisation of the nitrogen and sulfur atoms of the 4-quinolinyl and thien-2-yl rings to introduce a cationic nature was explored to improve the bioavailability of the drugs and uptake into the target cell walls for improved efficacy. Heavy Sn(IV) and In(III) central metal ions were introduced to enhance the singlet oxygen quantum yields and limit aggregation through axial ligation. The bromine atoms of the 4-bromo-thien-2-yl meso-aryl rings were also introduced to enhance the singlet oxygen quantum yields of the dyes. Furthermore, the utility of the porphyrin and corrole molecules for optical limiting properties to limit laser radiation to protect optical devices, including eyes, was explored by the z-scan technique. One of the dyes studied, Sn(IV) tetrathien-2-ylporphyrin, that exhibited the most favourable reverse saturable absorbance (RSA) response was embedded into a poly(bisphenol carbonate A) polymer thin film to further explore its suitability for practical applications. , Thesis (MSc) -- Faculty of Science, Chemistry, 2023
- Full Text:
- Date Issued: 2023-10-13
Dual and targeted photodynamic therapy ablation of bacterial and cancer cells using phthalocyanines and porphyrins in the presence of carbon-based nanomaterials
- Authors: Openda, Yolande Ikala
- Date: 2022-10-14
- Subjects: Phthalocyanines , Porphyrins , Active oxygen , Biofilms , Breast Cancer Treatment , Nanostructured materials , Combination therapy , Photochemotherapy
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/365945 , vital:65804 , DOI https://doi.org/10.21504/10962//365946
- Description: Phthalocyanines (Pcs) and porphyrins bearing substituents that possess antibacterial/anticancer properties are used as photosensitizers (PS) for the first time in the work. For targeting specificity and improved photoactivity, the PSs were afterward functionalized with carbon nanomaterials such as graphene quantum dots (GQDs) and detonation nanodiamonds (DNDs) via covalent conjugation (amide or ester bonds) or by non-covalent conjugation (π-π stacking and electrostatic interactions). Furthermore, the PSs-DNDs nanoconjugates were conjugated to either chitosan-capped silver nanoparticles (CSAg) via amide bonds or to the bare silver nanoparticles (Ag NPs) using the silver- nitrogen affinity. The as-synthesized nanoconjugates were also fully characterized by spectroscopic and microscopic methods together with thermal analysis. The potential photocytotoxicity of the complexes alone and their nanoconjugates against S. aureus and/or E. coli planktonic and biofilm cultures has been evaluated in vitro. Compared to the non- quaternized PSs, the cationic analogs exhibited a higher photodynamic inactivation against the planktonic cells with log10 reduction values above 9 in the viable count using a concentration of ca. 1.25 μM following 30 min exposure to light (Light dose: 943 J/cm2 for Pcs and 250 mW/cm2 for porphyrins). Whereas, at a concentration of ca. 100 μM the cationic PSs showed complete eradication of biofilms upon 30 min exposure to light. As a result of conjugation to carbon-based nanomaterials and silver nanoparticles, the compounds proved to be more effective as they exhibited stronger antibacterial and anti-biofilm activities on the multi-drug resistant bacteria strains due to synergetic effect, compared to PSs alone. This suggests that the newly prepared nanohybrids (PS concentration ca. 100 μM) could be used as potential antimicrobial agents in the treatment of biofilm-related infections. The target nanoconjugates showed all the advantages of two different groups existing on a single entity. In light of the potential advantages of combined chemotherapy and photodynamic antimicrobial chemotherapy (PACT), this work reports for the first time the use of PACT-ciprofloxacin (CIP) dual therapy using selected indium quaternized PSs which showed higher photoactivity with complete eradication of both Gram-positive and Gram-negative bacteria biofilms at concentrations of 8 μM of PS versus 2 μg/mL of the antibiotic following 15 min irradiation time (light dose: 471 J/cm2 for Pcs and fluence: 250 mW/cm2 for porphyrins) on S. aureus. Whereas the total killing of E. coli was obtained when combining 8 or 16 μM of PS combined with 4 μg/mL of CIP. The combined treatment resulted in the complete eradication of the matured biofilms with the highest log10 reduction values of 7.05 and 7.20 on S. aureus and E. coli, respectively. Used as a model, positively charged dimethylamino-chalcone Pcs also exhibited interesting photodynamic therapy (PDT) activity against MCF-7 cancer cells giving IC50 values of 17.9 and 7.4 μM, respectively following 15 min irradiation. Additionally, the TD-B3LYP/LanL2DZ calculations were run on the dimethylaminophenyl- porphyrins to compare the singlet excitation energies of quaternized and non-quaternized porphyrins in vacuo. the study shows excellent agreement between time-dependent density- functional theory (TD-DFT) exciting energies and the experimental S1>S0 excitation energies. The small deviation observed between the calculated and experimental spectra arises from the solvent effect. The excitation energies observed in these UV-Vis spectra mostly originated from electron promotion between the highest occupied molecular orbital (HOMO) for the less intense band and the HOMO-1 for the most intense band of the ground states to the lower unoccupied molecular orbital (LUMO) of the excited states. , Thesis (PhD) -- Faculty of Science, Chemistry, 2022
- Full Text:
- Date Issued: 2022-10-14
- Authors: Openda, Yolande Ikala
- Date: 2022-10-14
- Subjects: Phthalocyanines , Porphyrins , Active oxygen , Biofilms , Breast Cancer Treatment , Nanostructured materials , Combination therapy , Photochemotherapy
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/365945 , vital:65804 , DOI https://doi.org/10.21504/10962//365946
- Description: Phthalocyanines (Pcs) and porphyrins bearing substituents that possess antibacterial/anticancer properties are used as photosensitizers (PS) for the first time in the work. For targeting specificity and improved photoactivity, the PSs were afterward functionalized with carbon nanomaterials such as graphene quantum dots (GQDs) and detonation nanodiamonds (DNDs) via covalent conjugation (amide or ester bonds) or by non-covalent conjugation (π-π stacking and electrostatic interactions). Furthermore, the PSs-DNDs nanoconjugates were conjugated to either chitosan-capped silver nanoparticles (CSAg) via amide bonds or to the bare silver nanoparticles (Ag NPs) using the silver- nitrogen affinity. The as-synthesized nanoconjugates were also fully characterized by spectroscopic and microscopic methods together with thermal analysis. The potential photocytotoxicity of the complexes alone and their nanoconjugates against S. aureus and/or E. coli planktonic and biofilm cultures has been evaluated in vitro. Compared to the non- quaternized PSs, the cationic analogs exhibited a higher photodynamic inactivation against the planktonic cells with log10 reduction values above 9 in the viable count using a concentration of ca. 1.25 μM following 30 min exposure to light (Light dose: 943 J/cm2 for Pcs and 250 mW/cm2 for porphyrins). Whereas, at a concentration of ca. 100 μM the cationic PSs showed complete eradication of biofilms upon 30 min exposure to light. As a result of conjugation to carbon-based nanomaterials and silver nanoparticles, the compounds proved to be more effective as they exhibited stronger antibacterial and anti-biofilm activities on the multi-drug resistant bacteria strains due to synergetic effect, compared to PSs alone. This suggests that the newly prepared nanohybrids (PS concentration ca. 100 μM) could be used as potential antimicrobial agents in the treatment of biofilm-related infections. The target nanoconjugates showed all the advantages of two different groups existing on a single entity. In light of the potential advantages of combined chemotherapy and photodynamic antimicrobial chemotherapy (PACT), this work reports for the first time the use of PACT-ciprofloxacin (CIP) dual therapy using selected indium quaternized PSs which showed higher photoactivity with complete eradication of both Gram-positive and Gram-negative bacteria biofilms at concentrations of 8 μM of PS versus 2 μg/mL of the antibiotic following 15 min irradiation time (light dose: 471 J/cm2 for Pcs and fluence: 250 mW/cm2 for porphyrins) on S. aureus. Whereas the total killing of E. coli was obtained when combining 8 or 16 μM of PS combined with 4 μg/mL of CIP. The combined treatment resulted in the complete eradication of the matured biofilms with the highest log10 reduction values of 7.05 and 7.20 on S. aureus and E. coli, respectively. Used as a model, positively charged dimethylamino-chalcone Pcs also exhibited interesting photodynamic therapy (PDT) activity against MCF-7 cancer cells giving IC50 values of 17.9 and 7.4 μM, respectively following 15 min irradiation. Additionally, the TD-B3LYP/LanL2DZ calculations were run on the dimethylaminophenyl- porphyrins to compare the singlet excitation energies of quaternized and non-quaternized porphyrins in vacuo. the study shows excellent agreement between time-dependent density- functional theory (TD-DFT) exciting energies and the experimental S1>S0 excitation energies. The small deviation observed between the calculated and experimental spectra arises from the solvent effect. The excitation energies observed in these UV-Vis spectra mostly originated from electron promotion between the highest occupied molecular orbital (HOMO) for the less intense band and the HOMO-1 for the most intense band of the ground states to the lower unoccupied molecular orbital (LUMO) of the excited states. , Thesis (PhD) -- Faculty of Science, Chemistry, 2022
- Full Text:
- Date Issued: 2022-10-14
Porphyrinoid dyes for photodynamic anticancer and antimicrobial therapy treatments
- Authors: Soy, Rodah Cheruto
- Date: 2023-10-13
- Subjects: Porphyrins , Corrole , Chlorin , Photochemotherapy , Active oxygen , Photophysics , Photosensitizing compounds
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/432252 , vital:72855 , DOI 10.21504/10962/432252
- Description: The search for alternative therapies and non-toxic photosensitizer drugs that can efficiently generate cytotoxic reactive oxygen species for biomedical applications, such as in alternative photodynamic therapy (PDT) for cancer treatment and photodynamic antimicrobial chemotherapy (PACT) for drug-resistant bacteria treatment is on the rise. Nevertheless, the lack of photosensitizer dyes that absorb light strongly within the therapeutic window (620−850 nm) that can locally target the tumor and bacterial cells and generate singlet oxygen efficiently are some of the main challenges in PDT and PACT treatment. This study sought to address the challenges that impede PDT and PACT from realizing their full potential by synthesizing a series of meso-aryltetrapyrrolic photosensitizer dyes that absorb light within the therapeutic window. These include meso-tetraarylporphyrin (Por), A3-type meso-triarylcorrole (Cor), meso-tetraarylchlorin (Chl), and N-confused meso-tetraarylporphyrin (NCP) dyes with 4-thiomethylphenyl (1), thien-3-yl (2), thien-2-yl (3), 5-bromo-thien-2-yl (4), 4-methoxyphenyl (5), 3-methoxyphenyl (6), 4-hydroxyphenyl (7) and 4-hydroxy-3-methoxyphenyl (8) meso-aryl rings. Por, Cor, Chl and NCP dyes and and their Ga(III), P(V), In(III) and/or Sn(IV) complexes with 1-8, 1-4, 5-8 and 5 meso-aryl rings were studied, along with two A2B-type Ga(III) meso-triarylcorroles with pentafluorophenyl rings at the A2 positions and 3,6-di-t-butyl-9H-carbazole (9) or N-butyl-4-carbazole (10) rings at the B position that were prepared in the laboratory of Prof. Xu Liang of Jiangsu University in the People’s Republic of China. The carbazole nitrogen of 10-GaCor was quaternized at Rhodes University with ethyl iodide to form a cationic species (10-GaCor-Q) for PDT and PACT activity studies. The structures of the synthesized dyes were confirmed using UV-visible absorption and 1H NMR spectroscopy, and MALDI-TOF-mass spectrometry. 1-4-InPor In(III) porphyrins, 1-4-PVCor, 1-4-GaCor A3 PV and GaIII corrole dyes were also conjugated to gold nanoparticles (AuNPs) and silver nanoparticles (AgNPs) via sulfur-gold and sulfur-silver affinities. The successful conjugation of the dyes onto the nanoparticles to form dye-AuNP or dye-AgNP nanoassemblies was confirmed using transmission electron microscopy (TEM), energy dispersive X-ray (EDX) spectroscopy, X-ray powered diffraction (XRD), and (X-ray photon spectroscopy) XPS. The photophysicochemical, photostability, and lipophilicity properties of the dyes and their PDT and PACT activities were investigated, and the structure-property relationships were analyzed. This was accomplished by analyzing the changes in the properties of the dyes due to the meso-aryl substituents, central ions, molecular symmetry, and heavy atom effects. Time-dependent-density functional theory (TD-DFT) calculations were also used to further probe the electronic and optical spectroscopic properties of the dyes. The analysis of the photophysicochemical, photostability, and lipophilicity data for the synthesized dyes demonstrated that there are inherent structure-property relationships for the dyes studied. The TD-DFT calculations also assisted in rationalizing the observed optical spectroscopic data for the dyes. The introduction of different meso-aryl substituents resulted in minor absorption spectral changes on the parent structures of the dyes due to their inductive and mesomeric effects, while the insertion of Ga(III), In(III), and Sn(IV) electropositive metal centers resulted in marked red shifts of the B bands due to favorable interactions with the porphyrin or porphyrinoid ligand core. The lower symmetries of the corrole, chlorin, and N-confused porphyrin dyes resulted in enhanced absorption properties within the therapeutic window relative to porphyrins. The heavy atom effect from the Ga(III), In(III), and Sn(IV) central ions, the meso-aryl groups, and the external heavy atom effect from the AuNPs and AgNPs significantly reduced the fluorescence quantum yield values of the dyes resulting in high singlet oxygen quantum yields. The dye complexes also exhibited properly balanced lipophilic properties and high photostabilities. The P(V) ion of the A3 PV corrole dyes reduced the aggregation effects, enhanced cellular uptake, and lowered the lipophilicity values relative to the A3 GaIII corrole dyes. The porphyrin and porphyrinoid complexes studied exhibited relatively low in vitro dark cytotoxicity toward MCF-7 cancer cells, which is enhanced for AuNP nanoconjugates of 1-InPor, 1-3-PVCor, and 1-3-GaCor. The dyes also have low in vitro dark cytotoxicity toward planktonic and biofilm cells of S. aureus and E. coli. The complexes also exhibited favorable PDT and PACT activities toward MCF-7 cancer cells, and planktonic and biofilm S. aureus and E. coli bacteria due to their high singlet oxygen quantum yields. AuNP and AgNP nanoconjugates of 1-4-InPor, 1-4-PVCor, and 1-4-GaCor exhibited enhanced PDT and PACT activities due to the favorable synergistic effects of nanoparticles. The PDT and PACT activities of A3 PV corrole dyes and the nanoconjugates of 1-4-PVCor are slightly higher than those of A3-type GaIII corroles and their nanoconjugates due to decreased aggregation effects and enhanced PS drug uptake. The cationic 10-GaCor-Q species also exhibit favorable PDT and PACT activities in contrast to the neutral 9-10-GaCor dyes due to enhanced PS drug penetration into the tumor or bacteria cells. The complexes also exhibited high Log10 reduction values for planktonic S. aureus suggesting that the dyes are highly efficient PS dyes. The activities of the complexes toward planktonic E. coli bacteria are moderate except for 10-GaCor-Q, 2-4-PVCor-AgNPs, and 5-8-SnChl chlorins exhibiting relatively favorable activity with > 3 Log10 CFU.mL−1 values. The dyes also exhibit moderate activities toward the S. aureus and E. coli biofilm cells, which are lower than for the planktonic cells, as shown by their lower Log10 reduction values. The data demonstrate that the low symmetry corrole, chlorin, and N-confused porphyrin complexes that absorb light strongly within the therapeutic window have significantly enhanced PDT and PACT activities relative to their porphyrin analogs. , Thesis (PhD) -- Faculty of Science, Chemistry, 2023
- Full Text:
- Date Issued: 2023-10-13
- Authors: Soy, Rodah Cheruto
- Date: 2023-10-13
- Subjects: Porphyrins , Corrole , Chlorin , Photochemotherapy , Active oxygen , Photophysics , Photosensitizing compounds
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/432252 , vital:72855 , DOI 10.21504/10962/432252
- Description: The search for alternative therapies and non-toxic photosensitizer drugs that can efficiently generate cytotoxic reactive oxygen species for biomedical applications, such as in alternative photodynamic therapy (PDT) for cancer treatment and photodynamic antimicrobial chemotherapy (PACT) for drug-resistant bacteria treatment is on the rise. Nevertheless, the lack of photosensitizer dyes that absorb light strongly within the therapeutic window (620−850 nm) that can locally target the tumor and bacterial cells and generate singlet oxygen efficiently are some of the main challenges in PDT and PACT treatment. This study sought to address the challenges that impede PDT and PACT from realizing their full potential by synthesizing a series of meso-aryltetrapyrrolic photosensitizer dyes that absorb light within the therapeutic window. These include meso-tetraarylporphyrin (Por), A3-type meso-triarylcorrole (Cor), meso-tetraarylchlorin (Chl), and N-confused meso-tetraarylporphyrin (NCP) dyes with 4-thiomethylphenyl (1), thien-3-yl (2), thien-2-yl (3), 5-bromo-thien-2-yl (4), 4-methoxyphenyl (5), 3-methoxyphenyl (6), 4-hydroxyphenyl (7) and 4-hydroxy-3-methoxyphenyl (8) meso-aryl rings. Por, Cor, Chl and NCP dyes and and their Ga(III), P(V), In(III) and/or Sn(IV) complexes with 1-8, 1-4, 5-8 and 5 meso-aryl rings were studied, along with two A2B-type Ga(III) meso-triarylcorroles with pentafluorophenyl rings at the A2 positions and 3,6-di-t-butyl-9H-carbazole (9) or N-butyl-4-carbazole (10) rings at the B position that were prepared in the laboratory of Prof. Xu Liang of Jiangsu University in the People’s Republic of China. The carbazole nitrogen of 10-GaCor was quaternized at Rhodes University with ethyl iodide to form a cationic species (10-GaCor-Q) for PDT and PACT activity studies. The structures of the synthesized dyes were confirmed using UV-visible absorption and 1H NMR spectroscopy, and MALDI-TOF-mass spectrometry. 1-4-InPor In(III) porphyrins, 1-4-PVCor, 1-4-GaCor A3 PV and GaIII corrole dyes were also conjugated to gold nanoparticles (AuNPs) and silver nanoparticles (AgNPs) via sulfur-gold and sulfur-silver affinities. The successful conjugation of the dyes onto the nanoparticles to form dye-AuNP or dye-AgNP nanoassemblies was confirmed using transmission electron microscopy (TEM), energy dispersive X-ray (EDX) spectroscopy, X-ray powered diffraction (XRD), and (X-ray photon spectroscopy) XPS. The photophysicochemical, photostability, and lipophilicity properties of the dyes and their PDT and PACT activities were investigated, and the structure-property relationships were analyzed. This was accomplished by analyzing the changes in the properties of the dyes due to the meso-aryl substituents, central ions, molecular symmetry, and heavy atom effects. Time-dependent-density functional theory (TD-DFT) calculations were also used to further probe the electronic and optical spectroscopic properties of the dyes. The analysis of the photophysicochemical, photostability, and lipophilicity data for the synthesized dyes demonstrated that there are inherent structure-property relationships for the dyes studied. The TD-DFT calculations also assisted in rationalizing the observed optical spectroscopic data for the dyes. The introduction of different meso-aryl substituents resulted in minor absorption spectral changes on the parent structures of the dyes due to their inductive and mesomeric effects, while the insertion of Ga(III), In(III), and Sn(IV) electropositive metal centers resulted in marked red shifts of the B bands due to favorable interactions with the porphyrin or porphyrinoid ligand core. The lower symmetries of the corrole, chlorin, and N-confused porphyrin dyes resulted in enhanced absorption properties within the therapeutic window relative to porphyrins. The heavy atom effect from the Ga(III), In(III), and Sn(IV) central ions, the meso-aryl groups, and the external heavy atom effect from the AuNPs and AgNPs significantly reduced the fluorescence quantum yield values of the dyes resulting in high singlet oxygen quantum yields. The dye complexes also exhibited properly balanced lipophilic properties and high photostabilities. The P(V) ion of the A3 PV corrole dyes reduced the aggregation effects, enhanced cellular uptake, and lowered the lipophilicity values relative to the A3 GaIII corrole dyes. The porphyrin and porphyrinoid complexes studied exhibited relatively low in vitro dark cytotoxicity toward MCF-7 cancer cells, which is enhanced for AuNP nanoconjugates of 1-InPor, 1-3-PVCor, and 1-3-GaCor. The dyes also have low in vitro dark cytotoxicity toward planktonic and biofilm cells of S. aureus and E. coli. The complexes also exhibited favorable PDT and PACT activities toward MCF-7 cancer cells, and planktonic and biofilm S. aureus and E. coli bacteria due to their high singlet oxygen quantum yields. AuNP and AgNP nanoconjugates of 1-4-InPor, 1-4-PVCor, and 1-4-GaCor exhibited enhanced PDT and PACT activities due to the favorable synergistic effects of nanoparticles. The PDT and PACT activities of A3 PV corrole dyes and the nanoconjugates of 1-4-PVCor are slightly higher than those of A3-type GaIII corroles and their nanoconjugates due to decreased aggregation effects and enhanced PS drug uptake. The cationic 10-GaCor-Q species also exhibit favorable PDT and PACT activities in contrast to the neutral 9-10-GaCor dyes due to enhanced PS drug penetration into the tumor or bacteria cells. The complexes also exhibited high Log10 reduction values for planktonic S. aureus suggesting that the dyes are highly efficient PS dyes. The activities of the complexes toward planktonic E. coli bacteria are moderate except for 10-GaCor-Q, 2-4-PVCor-AgNPs, and 5-8-SnChl chlorins exhibiting relatively favorable activity with > 3 Log10 CFU.mL−1 values. The dyes also exhibit moderate activities toward the S. aureus and E. coli biofilm cells, which are lower than for the planktonic cells, as shown by their lower Log10 reduction values. The data demonstrate that the low symmetry corrole, chlorin, and N-confused porphyrin complexes that absorb light strongly within the therapeutic window have significantly enhanced PDT and PACT activities relative to their porphyrin analogs. , Thesis (PhD) -- Faculty of Science, Chemistry, 2023
- Full Text:
- Date Issued: 2023-10-13
Photodynamic anticancer and antimicrobial activities of aza-BODIPY and porphyrinbased photosensitisers and their non-linear properties
- Authors: Molupe, Nthabeleng Regina
- Date: 2024-10-11
- Subjects: Photochemotherapy , Anti-infective agents , Nonlinear optics , Cancer Treatment , BODIPY , Porphyrins
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/466603 , vital:76758 , DOI https://doi.org/10.21504/10962/466603
- Description: New aza-BODIPY dyes and porphyrins were synthesised and characterised so that photodynamic therapy (PDT) and photodynamic antimicrobial chemotherapy (PACT) activity studies could be performed. Several strategies were explored to achieve targeted nanoplatforms or biocompatible nanoplatforms to enhance the suitability of these compounds for use in PDT. Following earlier MSc research on the encapsulation of halogenated boron dipyrromethene (BODIPY) dyes into Pluronic® micelles, similar nanomicelles were prepared to encapsulate halogenated boron aza-dipyrromethene (aza-BODPY) dyes to enhance their aqueous solubility. However, the 1,7-dimethylthiophenyl- 2,6-diiodo-3,5-diphenyl (1) and 1,7-di-methylthiophenyl-2,6-diiodo- 3,5-dithien-3-yl (2) aza-BODIPY dyes that were prepared in this context were found to degrade when encapsulated. A different strategy was then followed in which gold nanoparticles (AuNPs) were conjugated to 1 and 2 via Au-S interactions to form biocompatible aza-BODIPY-AuNP conjugates (1-AuNP and 2-AuNP). This strategy was successful, and favourable IC50 values of 3.60 and 10.0 μM for 1-AuNP and 2- AuNP were obtained during in vitro PDT activity studies against MCF-7 human breast cancer cells, respectively, while values of 11.0 and 12.8 μM were obtained for 1 and 2. To further explore the preparation of better-targeted aza-BODIPY photosensitiser dyes, folic acid (FA) was conjugated to 1,7-dihydroxyphenyl-2,6-diiodo-3,5-di-4- bromophenyl (3) and 1,7-di-4-bromo-2,6-diiodo-3,5-dihydroxyphenylphenyl (4) aza- BODIPYs via ester bonds. Not only was the conjugation to form 3-FA and 4-FA successful, but the conjugated dyes are water-soluble, which is advantageous for drug transport in the context of PDT. These conjugates were applied in vitro against MCF-7 cancer cells and were found to have relatively high activities with IC50 values of 0.91 and 7.48 μM for 3-FA and 4-FA, respectively, while values of 11.3 and 13.0 μM were obtained for the non-conjugated 3 and 4 dyes. In a similar manner, tin (IV) and indium (III) tetrapyridylporphyrins (5 and 6) were axially conjugated to folic acid via ester bonds (5-FA and 6-FA). The conjugation was successful and enhanced the PDT activities of the dyes MCF-7 cancer cells in vitro from 48.2 to 29.6 μM for 5 and 5-FA, and from 43.9 to 13.3 μM for 6 and 6-FA. Relatively high dark toxicity was observed for 6-FA of 26.1 μM. When the nitrogen atoms of the meso-pyridyl rings were quaternized (5-FAQ and 6-FAQ) to further enhance the aqueous solubility of the complexes, it was not possible to calculate an IC50 value. When octanol-water partition coefficients (Log P) were calculated by the shake flask method, values of −0.70 and −1.70 were obtained for 5-FAQ and 6-FAQ, respectively. This provides evidence that the dyes are too water-soluble and not sufficiently lipophilic. The PACT activity properties of the synthesised diiodinated aza-BODIPYs were studied against Staphylococcus aureus (S. aureus) through photoirradiation for 60 min with Thorlabs M660L4 (280 mW.cm−2) and M730L4 (160 mW.cm−2) light emitting diodes (LEDs) mounted on the illumination chamber of Modulight® 7710-680 medical laser system providing doses at the well-plate of 100 and 57 J.cm−2.min−1. Aza- BODIPYs 2, 3 and 4 all inhibited the growth of S. aureus but with relatively low Log10 reductions of 1.37, 1.20 and 0.20. In contrast, aza-BODIPY 1 was found to have a Log10 reduction of 7.82. The PACT activities of free base and Sn(IV) 5-[4-(3- bromoethylcarboxyamidyl)phenyl]-10,15,20-triphenylporphyrins (7 and 8) prepared by Dr Balaji Babu (New Journal of Chemistry 2022, 46, 5288-5295) were tested against S. aureus to determine whether adding a triphenylphosphonium moiety to form free base and Sn(IV) 5-[4-(triphenylphosphonium)ethylcarboxyamidyl)phenyl]-10,15,20- triphenylporphyrin (18 and 19) enhances the photo-induced antibacterial activity, in addition to optimising the PDT properties due to its mitochondria-targeting properties. The PACT activities obtained against S. aureus were not favourable, but 18 exhibited enhanced activity across the studied concentration range. The potential utility of aza-BODIPY dyes 1-4 and their non-iodinated analogues (1a- 4a) for optical limiting applications was analysed by carrying out a series of Z-scan measurements, since dyes of this type have large ground state dipole moments, and this can enhance the non-linear optical limiting response. All the aza-BODIPY dyes under investigation exhibited intense non-linear absorption (NLA) behaviour with Zscan profiles that contain significant reverse saturable absorption (RSA) responses. Aza-BODIPYs 1, 2a, 2, 3, 4a, and 4 decreased the transmitted intensity of the strong laser beam to less than 50% of the linear response in organic solutions with a fixed absorbance of 1.8 for the main aza-BODIPY spectral band and a laser pulse input energy of 42 μJ. Higher second-order hyperpolarizability (γ) values were obtained for iodinated dyes 1, 2, 3 and 4. The highest value of 3.15×10−29 esu was obtained for 1. A comparative study involving the four non-iodinated dyes 1, 2, 3 and 4 and seven 1,3,5,7-tetraaryl aza-BODIPY dyes reported previously in the PhD thesis of Gugu Kubheka at Rhodes University demonstrated that there was no clear trend correlation between the γ values calculated from the Z-scan measurements and calculated dipole moments. , Thesis (PhD) -- Faculty of Science, Chemistry, 2024
- Full Text:
- Date Issued: 2024-10-11
- Authors: Molupe, Nthabeleng Regina
- Date: 2024-10-11
- Subjects: Photochemotherapy , Anti-infective agents , Nonlinear optics , Cancer Treatment , BODIPY , Porphyrins
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/466603 , vital:76758 , DOI https://doi.org/10.21504/10962/466603
- Description: New aza-BODIPY dyes and porphyrins were synthesised and characterised so that photodynamic therapy (PDT) and photodynamic antimicrobial chemotherapy (PACT) activity studies could be performed. Several strategies were explored to achieve targeted nanoplatforms or biocompatible nanoplatforms to enhance the suitability of these compounds for use in PDT. Following earlier MSc research on the encapsulation of halogenated boron dipyrromethene (BODIPY) dyes into Pluronic® micelles, similar nanomicelles were prepared to encapsulate halogenated boron aza-dipyrromethene (aza-BODPY) dyes to enhance their aqueous solubility. However, the 1,7-dimethylthiophenyl- 2,6-diiodo-3,5-diphenyl (1) and 1,7-di-methylthiophenyl-2,6-diiodo- 3,5-dithien-3-yl (2) aza-BODIPY dyes that were prepared in this context were found to degrade when encapsulated. A different strategy was then followed in which gold nanoparticles (AuNPs) were conjugated to 1 and 2 via Au-S interactions to form biocompatible aza-BODIPY-AuNP conjugates (1-AuNP and 2-AuNP). This strategy was successful, and favourable IC50 values of 3.60 and 10.0 μM for 1-AuNP and 2- AuNP were obtained during in vitro PDT activity studies against MCF-7 human breast cancer cells, respectively, while values of 11.0 and 12.8 μM were obtained for 1 and 2. To further explore the preparation of better-targeted aza-BODIPY photosensitiser dyes, folic acid (FA) was conjugated to 1,7-dihydroxyphenyl-2,6-diiodo-3,5-di-4- bromophenyl (3) and 1,7-di-4-bromo-2,6-diiodo-3,5-dihydroxyphenylphenyl (4) aza- BODIPYs via ester bonds. Not only was the conjugation to form 3-FA and 4-FA successful, but the conjugated dyes are water-soluble, which is advantageous for drug transport in the context of PDT. These conjugates were applied in vitro against MCF-7 cancer cells and were found to have relatively high activities with IC50 values of 0.91 and 7.48 μM for 3-FA and 4-FA, respectively, while values of 11.3 and 13.0 μM were obtained for the non-conjugated 3 and 4 dyes. In a similar manner, tin (IV) and indium (III) tetrapyridylporphyrins (5 and 6) were axially conjugated to folic acid via ester bonds (5-FA and 6-FA). The conjugation was successful and enhanced the PDT activities of the dyes MCF-7 cancer cells in vitro from 48.2 to 29.6 μM for 5 and 5-FA, and from 43.9 to 13.3 μM for 6 and 6-FA. Relatively high dark toxicity was observed for 6-FA of 26.1 μM. When the nitrogen atoms of the meso-pyridyl rings were quaternized (5-FAQ and 6-FAQ) to further enhance the aqueous solubility of the complexes, it was not possible to calculate an IC50 value. When octanol-water partition coefficients (Log P) were calculated by the shake flask method, values of −0.70 and −1.70 were obtained for 5-FAQ and 6-FAQ, respectively. This provides evidence that the dyes are too water-soluble and not sufficiently lipophilic. The PACT activity properties of the synthesised diiodinated aza-BODIPYs were studied against Staphylococcus aureus (S. aureus) through photoirradiation for 60 min with Thorlabs M660L4 (280 mW.cm−2) and M730L4 (160 mW.cm−2) light emitting diodes (LEDs) mounted on the illumination chamber of Modulight® 7710-680 medical laser system providing doses at the well-plate of 100 and 57 J.cm−2.min−1. Aza- BODIPYs 2, 3 and 4 all inhibited the growth of S. aureus but with relatively low Log10 reductions of 1.37, 1.20 and 0.20. In contrast, aza-BODIPY 1 was found to have a Log10 reduction of 7.82. The PACT activities of free base and Sn(IV) 5-[4-(3- bromoethylcarboxyamidyl)phenyl]-10,15,20-triphenylporphyrins (7 and 8) prepared by Dr Balaji Babu (New Journal of Chemistry 2022, 46, 5288-5295) were tested against S. aureus to determine whether adding a triphenylphosphonium moiety to form free base and Sn(IV) 5-[4-(triphenylphosphonium)ethylcarboxyamidyl)phenyl]-10,15,20- triphenylporphyrin (18 and 19) enhances the photo-induced antibacterial activity, in addition to optimising the PDT properties due to its mitochondria-targeting properties. The PACT activities obtained against S. aureus were not favourable, but 18 exhibited enhanced activity across the studied concentration range. The potential utility of aza-BODIPY dyes 1-4 and their non-iodinated analogues (1a- 4a) for optical limiting applications was analysed by carrying out a series of Z-scan measurements, since dyes of this type have large ground state dipole moments, and this can enhance the non-linear optical limiting response. All the aza-BODIPY dyes under investigation exhibited intense non-linear absorption (NLA) behaviour with Zscan profiles that contain significant reverse saturable absorption (RSA) responses. Aza-BODIPYs 1, 2a, 2, 3, 4a, and 4 decreased the transmitted intensity of the strong laser beam to less than 50% of the linear response in organic solutions with a fixed absorbance of 1.8 for the main aza-BODIPY spectral band and a laser pulse input energy of 42 μJ. Higher second-order hyperpolarizability (γ) values were obtained for iodinated dyes 1, 2, 3 and 4. The highest value of 3.15×10−29 esu was obtained for 1. A comparative study involving the four non-iodinated dyes 1, 2, 3 and 4 and seven 1,3,5,7-tetraaryl aza-BODIPY dyes reported previously in the PhD thesis of Gugu Kubheka at Rhodes University demonstrated that there was no clear trend correlation between the γ values calculated from the Z-scan measurements and calculated dipole moments. , Thesis (PhD) -- Faculty of Science, Chemistry, 2024
- Full Text:
- Date Issued: 2024-10-11
Photodynamic anticancer and antimicrobial activities of novel bacteriochlorins
- Tauyakhale, Kaisano Goodness
- Authors: Tauyakhale, Kaisano Goodness
- Date: 2024-10-11
- Subjects: Bacteriochlorin , Porphyrins , Photochemotherapy , Photophysics , Molecules Models , Active oxygen
- Language: English
- Type: Academic theses , Master's theses , text
- Identifier: http://hdl.handle.net/10962/464587 , vital:76524
- Description: The World Health Organization cautioned that the major contributing factors of cancer amongst people are the excessive usage of alcohol, smoking, lack of exercise and low intake of fruits, vegetables, and high-fibre foods. Furthermore, cancer by far is reported to be the most common and leading cause of death worldwide (1 in 6 deaths is due to cancer). Moreover, it is reported that cancer kills more people than tuberculosis, malaria and AIDS combined every year. Chemotherapy has been utilised as a mode of rehabilitation for complete being used in conjunction with surgery or to improve the state of well-being of patients until their point of death. However, it is well known for its adverse effects, such as loss of hair, altered gastric metabolism, vomiting and nausea, dehydration, weight loss, and loss of appetite. For this reason, photodynamic therapy (PDT) was developed as an alternative. A molecular dye (photosensitiser/PS) and light of a specific wavelength produce cytotoxic singlet oxygen species, which induce cell death. The aim of this project is to prepare novel structurally modified porphyrin-type dyes that absorb far into the near-infrared region. Identifying suitable dyes that absorb significantly in the 700−800 nm region is particularly important from an African perspective, since melanin significantly limits the penetration of laser light into human tissue in the 600−700 nm region, where first- and second-generation photosensitiser dyes usually absorb. The porphyrin analogues that will be investigated in this regard are bacteriochlorins (BChls), which are known to have suitable optical properties that are potentially suitable in this regard. The first step of the study would be to synthesise tetraarylporphyrins with electron- withdrawing meso-aryl rings because their reduction to BChls is more readily attainable than is the case with electron-donating rings. However, these contrasting properties can be combined to tailor the BChls for effective photodynamic therapy, so the type of porphyrins synthesised will be tetraarylBChls with different meso-aryl groups to first analyze the induction of different chemical properties in this case, the impact of introducing electron donating (4- and 3-quinoline substituents) or electron-withdrawing (pentafluorophenyl substituents) groups on the meso-positions of the dyes and more specifically whether the position of the quinoline nitrogen atom relative to the core of the BChl has any significant impact on the reactivity of the dye (the 4- or 3-position of the quinoline). The next factor to be considered is the induction of the heavy atom effect by introducing a metal in the centre of the dye in order to try to increase the singlet oxygen quantum yields for high production of reactive oxygen species and singlet oxygen and further red shift the lowest energy absorption band of the BChls in the therapeutic window for deep tissue penetration for effective. Lastly, the goal will be to explore whether the delivery of bacteriochlorin photosensitisers to cancer cells can be enhanced by introducing quaternised nitrogen atoms to the meso-aryl ligands. , Thesis (MSc) -- Faculty of Science, Chemistry, 2024
- Full Text:
- Date Issued: 2024-10-11
- Authors: Tauyakhale, Kaisano Goodness
- Date: 2024-10-11
- Subjects: Bacteriochlorin , Porphyrins , Photochemotherapy , Photophysics , Molecules Models , Active oxygen
- Language: English
- Type: Academic theses , Master's theses , text
- Identifier: http://hdl.handle.net/10962/464587 , vital:76524
- Description: The World Health Organization cautioned that the major contributing factors of cancer amongst people are the excessive usage of alcohol, smoking, lack of exercise and low intake of fruits, vegetables, and high-fibre foods. Furthermore, cancer by far is reported to be the most common and leading cause of death worldwide (1 in 6 deaths is due to cancer). Moreover, it is reported that cancer kills more people than tuberculosis, malaria and AIDS combined every year. Chemotherapy has been utilised as a mode of rehabilitation for complete being used in conjunction with surgery or to improve the state of well-being of patients until their point of death. However, it is well known for its adverse effects, such as loss of hair, altered gastric metabolism, vomiting and nausea, dehydration, weight loss, and loss of appetite. For this reason, photodynamic therapy (PDT) was developed as an alternative. A molecular dye (photosensitiser/PS) and light of a specific wavelength produce cytotoxic singlet oxygen species, which induce cell death. The aim of this project is to prepare novel structurally modified porphyrin-type dyes that absorb far into the near-infrared region. Identifying suitable dyes that absorb significantly in the 700−800 nm region is particularly important from an African perspective, since melanin significantly limits the penetration of laser light into human tissue in the 600−700 nm region, where first- and second-generation photosensitiser dyes usually absorb. The porphyrin analogues that will be investigated in this regard are bacteriochlorins (BChls), which are known to have suitable optical properties that are potentially suitable in this regard. The first step of the study would be to synthesise tetraarylporphyrins with electron- withdrawing meso-aryl rings because their reduction to BChls is more readily attainable than is the case with electron-donating rings. However, these contrasting properties can be combined to tailor the BChls for effective photodynamic therapy, so the type of porphyrins synthesised will be tetraarylBChls with different meso-aryl groups to first analyze the induction of different chemical properties in this case, the impact of introducing electron donating (4- and 3-quinoline substituents) or electron-withdrawing (pentafluorophenyl substituents) groups on the meso-positions of the dyes and more specifically whether the position of the quinoline nitrogen atom relative to the core of the BChl has any significant impact on the reactivity of the dye (the 4- or 3-position of the quinoline). The next factor to be considered is the induction of the heavy atom effect by introducing a metal in the centre of the dye in order to try to increase the singlet oxygen quantum yields for high production of reactive oxygen species and singlet oxygen and further red shift the lowest energy absorption band of the BChls in the therapeutic window for deep tissue penetration for effective. Lastly, the goal will be to explore whether the delivery of bacteriochlorin photosensitisers to cancer cells can be enhanced by introducing quaternised nitrogen atoms to the meso-aryl ligands. , Thesis (MSc) -- Faculty of Science, Chemistry, 2024
- Full Text:
- Date Issued: 2024-10-11
- «
- ‹
- 1
- ›
- »